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KMID : 0882420100780030333
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Korean Journal of Medicine
2010 Volume.78 No. 3 p.333 ~ p.340
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p16INK4A promoter hypermethylation and expression of p16INK4A, cyclin D1, and Rb in papillary thyroid carcinoma
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Kim Yun-Jung
Kim Hye-Soon
Hah Yu-Jin
Lee Ho-Young
Park Keun-Gyu
Kim Mee-Kyoung
Kwon Sun-Young
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Abstract
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Background/Aims: Dysregulation of the cell cycle is believed to be important in human neoplasia. p16INK4a, a regulator of the retinoblastoma protein, is inactivated by several mechanisms, including hypermethylation of the promoter. The aim of this study was to assess the relationship between p16INK4a methylation status and the expression of p16INK4a, cyclin D1, and retinoblastoma protein in papillary thyroid cancer.
Methods: Thirty-five surgically resected papillary thyroid cancer cases treated at Keimyung University Dongsan Medical Center from Jan 2003 to Dec 2005 were included in the study. We examined promoter hypermethylation of p16INK4a and immunohistochemically analyzed p16INK4a, cyclin D1, and retinoblastoma protein expression.
Results: Aberrant hypermethylation of 5’ CpG islands of the p16INK4a gene promoter was observed in 17 (48.6%) out of 35 cases, and the p16INK4a protein was lost in 18 (51.4%) cases. With the exception of one case, p16INK4a promoter hypermethylation correlated with the loss of p16INK4a protein expression (p<0.0001). Overexpression of cyclin D1 was found in 27 (77.1%) cases and retinoblastoma immunostaining was detected in 10 (28.6%) cases. There was an inverse relationship between p16INK4a and pRb immunostaining (p<0.018, r=-0.398), and a strong direct correlation between cyclin D1 and pRb immunostaining (p<0.0001, r=0.710). Cyclin D1 expression was significantly associated with the pathologic T stage of cancer (p=0.04).
Conclusions: These data suggest that promoter hypermethylation is a major mechanism underlying the inactivation of p16INK4a and alterations in the p16 INK4a/cyclin D1/retinoblastoma pathway, which are thought to be very important in papillary thyroid cancer.
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KEYWORD
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Cyclin D1, Methylation, p16INK4a, Retinoblastoma, Thyroid Neoplasm
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